Pengantar Bioteknologi

FARMASI UTA
2013
Priyo Wahyudi
 Pengantar Bioteknologi
Definisi bioteknologi
Ruang lingkup bioteknologi
Sejarah bioteknologi
State of the art bioteknologi
Nilai strategis biotek (now & future).
 Bioteknologi
Dari akar kata:
BIO = mahluk hidup, proses yang terjadi pada mahluk hidup
TEKNOLOGI = kumpulan teknik untuk memecahkan masalah
atau membuat produk yang bermanfaat
3 Kata Kunci Bioteknologi:
1. Bios (materi hidup) yang meliputi : Virus, Bakteri, Fungi,
Tanaman dan Hewan
2. Sains dan teknologi, merupakan integrasi keduanya
3. Menghasilkan Produk atau Jasa, bagi kesejahteraan hidup
manusia
Bioteknologi merupakan pengintegrasian beberapa
disiplin ilmu pengetahuan alam dan teknologi :
Mikrobiologi, Fisiologi, Biokimia, Genetika, Biologi
Molekuler, Kimia serta rekayasa proses dan Teknik
kimia.
Output Process Input
Produk Sains & Bio
atau Teknologi
Jasa
3 Kata Kunci Bioteknologi
 Komponen Bio
Organisme utuh : virus, sel bakteri, sel fungi, sel
alga, sel protozoa, individu tanaman, individu hewan,
manusia.
Bagian / komponen organisme : protein envelope,
protein capsid, protein core, dinding sel, flagela, pili,
ribosom, DNA, RNA
Produk metabolit dari organisme : metabolit
primer & sekunder
Agen biokonversi dari organisme : enzim ,
hormon, imunoglobulin
Bahan baku (raw material) yang berasal dari
organisme : tepung jagnng, tepung tapioka,
cangkang kepiting, kulit udang
 Integrasi Ilmu & Teknologi dalam
Bioteknologi

Crops Drugs Vaccines Diagnostics Livestock

 Integrasi Ilmu & Teknologi
Perkembangan BIOTEKNOLOGI akan ditentukan
kemajuan di bidang:
SAINS: TEKNOLOGI :

BIOLOGI MOLEKULER TEKNIK KIMIA

GENETIKA TEKNIK MESIN
MIKROBIOLOGI TEKNIK ELEKTRO
FISIOLOGI TEKNIK INFORMATIKA
KIMIA
FARMASI
EKONOMI
MATERIAL
KOMPUTER
 Output Bioteknologi
Produk :
1. Makanan: keju, yoghurt, tempe, kecap, tauco, tape, oncom, tape,
ketan brem, arak, tuak, wine, beer, terasi, nata
2. Obat-obatan: antibiotik, hormon, vaksin, vitamin, antibodi monoklonal
3. Pertanian: pupuk bio, pestisida bio, kompos, bibit tanaman unggul
4. Peternakan: sapi daging, sapi susu, ayam daging, ayam telor, domba
wol,
5. Fuel : bio etanol
6. Metabolit tanaman
7. Fragrance
8. Senjata biologis : toksin antrax, virus cacar
Jasa :
1. Pengolahan limbah cair
2. Pengolahan limbah padat kompos
3. Penanganan pencemaran minyak di laut
4. Forensik
5. Diagnostik
 Definisi Bioteknologi
Bioteknologi adalah integrasi ilmu pengetahuan
alam dan engineering untuk mendapatkan produk
dan servis dari organisme, sel, bagian darinya
dan molekul-molekul analognya (European
Federation of Biotechnology, 1989)
Bioteknologi adalah penggunaan organisme hidup
atau teknik biologis dalam industri yang
dikembangkan melalui penelitian dasar (Biotech
Life Sciences Dictionary)
Bioteknologi adalah suatu bidang penerapan
biosains dan teknologi yang menyangkut
penerapan praktis organisme hidup atau
komponen subselulernya pada industri jasa dan
manufaktur serta pengelolaan lingkungan (Smith,
 Ruang Lingkup
Bioteknologi
Bioteknologi telah menjadi bagian dari kehidupan
sehari-hari manusia, yang meliputi produk bahan
pangan yang kita makan, obat yang kita minum,
dan tanaman yang kita tanam, serta mengelola
lingkungan kita.
Sejak ditemukannya struktur DNA, lompatan besar
telah dibuat dalam memahami mekanisme fungsi
sel, metabolisme, replikasi dan pembentukan
produk. Keuntungan ilmiah dari rekayasa genetika
dan biologi molekuler berlanjut dengan kecepatan
yang makin tinggi. Kemajuan ini membawa peluang
dalam menciptakan industri-industri baru yang
didasarkan pada sel hidup dan komponen sel.
Bioteknologi digunakan dalam aktivitas yang
 Ruang Lingkup Bioteknologi
1. Pertanian Agronomi, Perikanan,
Peternakan
2. Pangan & Gizi
3. Farmasi
4. Medis & Kesehatan
5. Industri Kimia
6. Lingkungan
7. Militer
8. Material
9. Energi
 Ruang Lingkup Bioteknologi
1. Pertanian Agronomi, Perikanan, Peternakan
Pemuliaan tanaman untuk meningkatkan
resistensi terhadap hama, penyakit, kekeringan
dan kondisi kadar garam tinggi
Perbanyakan massal dari bibit tanaman
Pengembangan biopestisida
Modifikasi tanaman untuk meningkatkan
karakteristik nutrisi dan proses
Marker
Methods for Plant Genetic Engineering are Well-
Developed and Similar to Those for Animals
 Transgenic
Non-transgenic
 Biological Insecticides
Microbes that are
pathogenic to insects
are alternatives to
chemical pesticides in
preventing insect
damage to agricultural
crops and disease
transmission
Bacillus thuringiensis
infections are fatal in
many insects but
harmless to other
animals, including
humans, and to plants
Roundup Transgenic Plant
den Rice is Modified to be Provide a Dietary Source of Vitami

Golden rice
(yellow) with
standard rice
(white).
Worldwide, 7% of children suffer vitamin A deficiency,
many of them living in regions in which rice is a staple
 The Golden Rice Story
Vitamin A deficiency is a major health problem
Causes blindness
Influences severity of diarrhea, measles
>100 million children suffer from the problem

For many countries, the infrastructure doesnt exist

to deliver vitamin pills

Improved vitamin A content in widely consumed crops

an attractive alternative
 -Carotene Pathway in Plants
IPP

Geranylgeranyl diphosphate
Phytoene synthase

Phytoene
Problem: Phytoene desaturase
Rice lacks
these enzymes -carotene desaturase

Lycopene
Lycopene-beta-cyclase
Normal
Vitamin A -carotene
Deficient
Rice (vitamin A precursor)
 The Golden Rice Solution
-Carotene Pathway Genes Added
IPP

Geranylgeranyl diphosphate
Daffodil gene Phytoene synthase

Phytoene
Vitamin A Phytoene desaturase
Pathway Single bacterial gene;
performs both functions
is complete -carotene desaturase
and functional Lycopene
Daffodil gene Lycopene-beta-cyclase

Golden -carotene
Rice (vitamin A precursor)
 Ruang Lingkup Bioteknologi
Perikanan & Peternakan
Produksi vaksin
Pengendalian fertilitas
Persilangan hewan ternak
Kloning
Pembenihan Tuna

Ikan salmon hasil rekayasa genetik (biotech) salmon (left)

dan standard salmon (right).
 Ruang Lingkup Bioteknologi
2. Pangan & Gizi
Produksi roti, keju, yoghurt dan pangan
fermentasi seperti cuka dan kecap
Pembuatan keju, tempe dan sosis
Pembuatan bir dan wine
Produksi flavour dan bahan pewarna
 Ruang Lingkup Bioteknologi
3. Farmasi
Pengembangan molekul baru untuk pengobatan
(novel therapeutic molecules for medical
treatments)
Pembuatan diagnostic kits
Sistem delivery obat
Penicillin fermentation
Recombinant DNA Tech Human
Insulin Production by Bacteria
 Human Insulin Production by Bacteria

and cut with a restriction enzyme

6) join the plasmid and human fragment

 Human Insulin Production by Bacteria

Mix the recombinant plasmid with

bacteria.

Screening bacterial cells to learn which contain the

human insulin gene is the hard part.
 Route to the Production by Bacteria of Human Insulin
One cell with the
recombinant plasmid

A fermentor used to grow

recombinant bacteria.

This is the step when gene cloning takes place.

The single recombinant plasmid replicates within a cell.
Then the single cell with many recombinant
plasmids produces trillions of like cells with
recombinant plasmid and the human insulin
 Route to the Production by Bacteria of Human Insulin

The final steps are to collect the bacteria, break open

the cells, and purify the insulin protein expressed
from the recombinant human insulin gene.
Rapid test

37
38
 Test device component categories
Porous materials
Sample pads
Conjugate pads
Membranes Absorbent pads

Reagents
Capture antibodies and/or antigens (test line and control line)
Conjugate ligand (antibody or antigen)
Detector particle (e.g., colloidal gold)
Blocking agents, detergents, surfactants, stabilizers, buffers, etc.

Housing and lamination materials

Back laminate (for holding porous components together)
Top laminate (optional, to act as a "splash guard" or prevent
evaporation and back-migration of detector reagent)

Device housing (optionalif used, the housing typically comprises

two, snap-fit plastic pieces that envelop the reagent-loaded porous
media assembly and facilitate sample addition)

39
Rapid immunoassay

40
Rapid immunoassay

41
42
Rapid lateral flow test

43
Pregnancy
test

44
 Specifications for a pregnancy test
Following are the development guidelines given to the research and development
manager responsible for designing, developing, and scaling up to manufacturing a
hypothetical lateral-flow diagnostic test device for detecting human chorionic
gonadotropin (hCG) in urine.
The hCG hormone is measured in milli-international units per milliliter (mIU/ml).

More than 99% of specimens containing 25 mlU/ml will produce a visible signal at the
test line.

More than 99% of specimens containing 5 mlU/mL will not produce a visible signal at
the test line.

The test will have a control line that will always produce a visible signal if the test is
performed correctly and if all of the test components are functional.

If the sample is positive (contains 25 mIU/ml hCG), the test must produce a visible
signal at the test line within 3 minutes of sample addition.

The test result must be stable (not change) for at least 30minutes after the sample is
added.

The test device will be contained in a plastic housing and designed to be compatible
with "in-stream" sampling protocols.

The packaged (unused) product must be stable for at least 18 months at ambient
conditions (1530C).

Total incremental manufacturing cost per test (excluding licensing and royalties) can45
not exceed $0.25 US.
Rapid test for drugs of
abuse

46
47
 Ruang Lingkup Bioteknologi
4. Medis & Kesehatan
Rekayasa jaringan untuk mengganti organ
Stem cell
Terapi gen
Terapi Gen
 Terapi Gen

Andrew Gobea was diagnosed with ADA (Adenosin Deaminase) deficiency

before he was born. Without this enzyme, the body is unable to break down a
toxic substance called deoxyadenosine. The toxin builds up and destroys
infection-fighting immune cells called T and B lymphocytes.
This lack of the ADA enzyme causes an immune deficiency disease called
SCID (Severe Combined immunodeficiency).
Andrew was given the gene for a functional ADA enzyme four days after his
birth in 1993.
 Umbilical cord blood was collected at birth.
Stem cells were isolated and mixed with a virus carrying a functional ADA
gene.
Stem cells were returned to Andrew with the aim of populating his bone
marrow with cells that could make the ADA enzyme.
 Two Years Later

Andrew has been maintained on costly injections of purified

ADA enzyme while waiting to see if the gene therapy has been
effective.
Tests have shown that the functional ADA gene was introduced
into 0.01% of Andrews stem cells and this population has given
rise to 5-7% of his white blood cells. Is this enough for a cure?
 Four Years Later
Andrews physician decides to taper off the enzyme injections to
see if Andrews immune system can protect him.
 Ruang Lingkup Bioteknologi
5. Industri Kimia
Produksi bahan kimia dan pelarut seperti
etanol, asam sitrat, aseton dan butanol
Sintesis bahan kimia adi seperti enzim, asam
amino, dan alkaloid
 Ruang Lingkup Bioteknologi
6. Lingkungan
Recovery biologis logam-logam berat dari limbah
pertambangan dan industri
Bioremediasi tanah dan air yang tercemar bahan
kimia beracun
Pengolahan sampah dan air limbah
Bioleaching
Biosensors: mendeteksi senyawa toksik di
lingkungan, contoh: RIS Water tests yi antibody
based kit to detect low level of solvents such as
benzene
A. ferrooxidans and its proposed
role in bioleaching. The
chemolithoautotrophic metabolism
of A. ferrooxidans results in the
oxidation/reduction of iron and sulfur
compounds and the solubilization of
copper and other commercially
valuable metals in a process called
bioleaching or biomining. It also
results in the production of acidified
solutions in pristine environments and
acid mine drainage in bioleaching
operations. A) Model of copper
bioleaching by A. ferrooxidans. B)
Oxidation/reduction reactions carried
out by A. ferrooxidans. The scheme
provided here presents the basic
concepts of bioleaching and further
details are provided in the review [4].
C) Acid mine drainage in the Rio
Tinto, Spain, derived from naturally
occurring pyritic ore bodies and
abandoned mine workings initiated in
pre-Roman times [3]. D) Commercial
bioleaching heap for copper recovery,
Chile. 3PG: 3-phosphoglycerate.
 Ruang Lingkup Bioteknologi
7. Militer
Senjata biokimia dan biologis
Biosensor anti toksin
Anti Bioterorisme
Forensik DNA
Applications of Biotechnology
for Identification: Forensics

1 2 3 CS 4 5 67
RC
I E
Suspects MN Suspects
EE
Applications of Biotechnology
for Identification: Paternity
Testing

X X

X X

X X

X X
 Ruang Lingkup Bioteknologi
8. Material
Biomaterial untuk operasi dan pembedahan
Biomaterial untuk otomotif
Biomaterial untuk akustik

Jaring laba-laba 5x lebih kuat dari

Artificial epidermis untuk operasi
baja dengan diameter yang sama
Bioselulosa (nata) dijadikan sebagai membran pada speaker
 Ruang Lingkup Bioteknologi
9. Energi
Biofuel Ethanol
Biodiesel
Biohidrogen fuel cell
5. Bio-fuels

Plant-derived fuels: plant

species for hydrocarbon (oil)
production, e.g. rape-seed,
sunflower, olive, peanut oils. Or
ethanol production of sugars (or
cellulose) derived from plants.
Conversion of used cooking oil to
bio-fuel (called bio-diesel)
Biogas: gases from composts or
landfill, but methane is a green
house gas
Bioethanol and biofuel cell:
Sugar cane, sugar beet wastes, high starch
material (cassava, potatoes, millet) to be
hydrolyzed by starch hydrolyzing enzyme to
convert sucrose or glucose to ethanol. Mainly
used in Brazil.
Corn ethanol: 22% less carbon emission, used in
the US.
Bio-diesel: 68% less carbon emission; oils from
soybean (US) or canola oil (Germany)
Cellulosic ethanol: 91% less carbon emission,
but difficult to change cellulose to ethanol
Hydrogen energy however is the trend of future
renewable energy without carbon emission: a
journey to forever.
 A Journey forever?
Various bacteria and algae, for example
Escherichia coli, Enterobacter aerogenes,
Clostridium butyricum, Clostridium
acetobutylicum, and Clostridium perfringens
have been found to be active in hydrogen
production under anaerobic conditions.
The most effective H2 production is observed
upon fermentation of glucose in the presence of
Clostridium butyricum (strain IFO 3847, 35
mmol h1 H2 evolution by 1 g of the
microorganism at 37C).
Fuel ethanol
 Hydrogen Fuel Cells
Fuel cells are similar
to batteries, but
designed for
continuous
replenishment of
energy via external
fuel
Many different types
of fuel cells, most
common will likely be
the PEM FC
Hydrogen and oxygen
in, water vapor and
liquid water out
Typical output is about
science of hydrogen fuel cells
A Pathway for our Future Energy?
 A microbial
biofuel cell:
(A) With a microbial
bioreactor providing
fuel separated from the
anodic compartment of
the electrochemical cell.

(B) With a microbial bioreactor

providing fuel directly in the anodic
compartment of the electrochemical
cell.
The Working principle Of An Enzyme Fuel Cell

The enzyme and mediator are immobilized on

the anode.

Rough layout of the anode structure

 General characteristics of chemical and biological fuel cell

Chemical Fuel Cell Biological Fuel Cell

Catalyst Noble Metals Microorganism /
enzyme
pH Acidic Solution Neutral Solution pH
(pH<1) 7.0-9.0
Temperature over 200 C Room Temperature
22-25 C
Electrolyte Phosphoric-acid Phosphate Solution
Capacity High Low
Efficiency 40 - 60 % over 40 %
Fuel Type Natural gas, H2, etc. Any Carbohydrates
and hydrocarbons
*conversion rate 50%
Theoretical energy content of methanol, ethanol,
and glucose. The calculation is based on the
assumption of complete conversion; the likely
conversion rate in practice is around 50 %.

Methanol Ethanol Glucose

(1 g/10 ml H2O) (1 g/10 ml H2O) (3 g /10 ml H2O)

Capacity [m Ah] 5025 (2512*) 3500 (1750*) 893 (446*)

H2O formed [g] 1.125 0.391 0.300
CO2 formed [g] 1.375 0.956 2.97 glucono-
lactone
 Fuel Cell Parts
Form and Function
 The Energy Problem
How will society
meet growing
energy demands in
a sustainable
manner?
Fossil-fuels
currently supply
~80% of world
energy demand.
Are Biofuels the Answer?...
 Biofuels as an Alternative
Biofuels are not THE answer to
sustainable energy, but biofuels may
be part of the answer
Biofuels may offer advantages over
fossil fuels, but the magnitude of
these advantages depends on how a
biofuel crop is grown and converted
into a usable fuel
 Analysis of Alternative
Biofuels
First generation biofuels: food-
based biofuels that are currently
commercially available:
Corn-grain ethanol
Soy Biodiesel
Second generation biofuels:
cellulosic biofuels of the future
Diverse prairie biomass
What is Biodiesel?
Alternative fuel for diesel engines
Made by chemically combining any natural
oil or fat (from vegetable oil or animal fat)
with an alcohol
Lower emissions, High flash point (>300F),
Safer
Biodegradable, Essentially non-toxic.
Chemically, biodiesel molecules
Fatty Acid
are mono-
alkyl
FA esters produced usually
Alcohol from
triglyceride esters Glycerin

FA FA

FA Biodiesel
Vegetable Oil
Bio diesel Process Flow
Diagram

NRRaje Feb 06
Biodiesel Samples
NRRaje Feb 06
 Milestone Bioteknologi
FERMENTASI
Proses kimiawi dari senyawa organik yang dimediasi oleh
enzim.
Fermentasi dikenal sejak 6000 SM (Sumeria dan Babilonia
membuat bir)
Bioteknologi tradisional Bioteknologi moderen
Disain Bioreaktor
Bidang: Pangan, produksi biomassa, antibiotika, enzim dll.

REKAYASA GENETIKA
Upaya merekayasa materi genetik organisme untuk
meningkatkan kemampuannya
RG pada mikroorganisme industri antibiotika, enzim dan
asam amino, dll
RG pada tanaman tanaman transgenik antihama (Bt
cotton / Bt corn), tanaman tahan kondisi lingkungan ekstrim
(tahan alkali, tahan garam, tahan logam berat, tahan
kekeringan), tanaman super dengan produksi yang berlipat
 Milestone Bioteknologi
TEKNOLOGI ENZIM
Enzim diproduksi oleh organisme (mikroorganisme, hewan dan
tumbuhan) diaplikasikan di industri makanan, minuman, manufaktur,
dll
Kompetensi enzim adalah mengurangi energi yang diperlukan untuk
terjadinya proses biokonversi
Perkembangan selanjutnya enzim mikroorganisme mendominasi
karena segi kemudahan produksinya
Enzim protease, karbohidrase, lipase, lainnya

REKAYASA BIOKIMIA
Proses biokimiawi dalam metabolisme mikroorganisme dapat
direkayasa Biokonversi / Biotransformasi

REKAYASA PRODUK / SISTEM

Produk molekul biologi seperti antibodi atau enzim dapat
dikembangkan sebagai BIOSENSOR untuk tujuan diagnosis dan
detoksifikasi
Perkembangan genetika molekuler memungkinkan pengobatan suatu
penyakit herediter ataupun degeneratif melalui terapi gen
Timeline Bioteknologi
 Timeline Bioteknologi
Awal mula manusia mengenal Bioteknologi dimulai sejak
10.000 tahun lalu pada awal peradaban pertanian (early
agrarian societies) dimana orang mengumpulkan benih
tanaman dengan sifat yang dikehendaki untuk ditanam
pada tahun berikutnya dan melakukan persilangan yang
selektif untuk meningkatkan kualitas hewan ternak, seperti
di Babylonia, Mesir dan Romawi.
Pada 6000 SM orang telah membuat bir, anggur dan roti
melalui fermentasi, sebuah proses alami dimana aktifitas
organisme bersel tunggal memainkan peran yang penting.
Pada 4000 SM di Cina telah menggunakan bakteri asam
laktat (BAL) untuk membuat yogurt, kapang untuk
membuat keju dan bakteri asam asetat untuk membuat
cuka.
Fermentasi Mesir Kuno
 Timeline Bioteknologi
Pada tahun 1500 sesudah masehi, ekspedisi
pengumpulan tanaman telah mencakup seluruh
penjuru dunia. Koleksi tersebut dapat membuat
Bank Gen
Nikolai Tanaman
I. Vavilov (1887 yang
1943)pertama.
ahli genetika
tanaman dan agronomi Russia menginisiasi
program riset dan persilangan yang
komprehensif yang mencakup suatu rencana
logis untuk manajemen sumber genetika
tanaman. Ia mengkoleksi hampir seluruh
jenistanamandi dunia yang kemudian
mengantarnya pada teori "asal-usul
penyebaran" tanaman budidaya. Selain itu,
ia juga mempelajari cara-cara memperbaiki
hasiljagung,gandum, danserealialainnya
untuk mendukung pertumbuhan penduduk
dunia.
 Timeline Bioteknologi

Akhir abad 19 merupakan sebuah tonggak

(milestone) dalam biologi. Gregor Mendel
(1822 - 1884) memulai studi genetika
 Timeline Bioteknologi
Istilah "BIOTEKNOLOGI" dimunculkan pertama
kali pada tahun 1917 oleh Karl Ereky (1878
1952), seorang insinyur Hungaria.
Produksi daging babi menggunakan gula bit sebagai
pakan
BIOTEKNOLOGI didefinisikan sebagai semua lini
pekerjaan yang dihasilkan dari raw material dengan
bantuan organisme
Bioteknologi hidup.di
diterapkan
industri dan pertanian
bersamaan pada awal abad
ke-20. Proses fermentasi
dikembangkan diantaranya
untuk memproduksi aseton
dari pati dan cairan cat
untuk mobil.
 Timeline Bioteknologi
Antara tahun 1930 - 1952,
peneliti memfokuskan
pada hubungan antara
gen dan protein. Mereka
menemukan suatu
hubungan langsung
antara mutasi sebuah gen
dan sekuens asam amino
dari sebuah protein.
Penemuan antibiotik
penisilin oleh Alexander
Fleming (1928) telah
membawa perkembangan
biteknologi ke arah
farmasi.
 A Fortunate Accident
Antibiotics
1928: Alexander
Fleming discovered
the first antibiotic
Fleming observed
that Penicillium
fungus made an
antibiotic, penicillin,
that killed S. aureus
1940s: Penicillin was
tested clinically and
mass produced
 Timeline Bioteknologi

Pada tahun 1961 Bioteknologi diredifinisi

sebagai industrialisasi produksi barang atau
jasa melalui suatu sistem dan proses biologis
pada suatu organisme

Bioengineered Biotechnology Process

Bioengineered Biotechnology
Process
Upstream processing
Preparation of raw
material
Fermentation and
biotransformation
Use of bioreactor
Downstream
processing
Recovery and
purification from the
medium or cell mass
 Timeline Biotechnology
In the 1960s and 1970s focused primarily on
improving upstream processing, bioreactor
design and downstream processing
New strains created by mutation and screening
Very successful for antibiotic production
Everything changes with development of
recombinant DNA technology
New organisms for production (transfer production to
new species)
Quantity production of molecules normally present at
miniscule levels
 Timeline Bioteknologi
1950 to 1960
1951 McClintock discovers transposable elements, or "jumping genes,"
in corn.
1953 Watson and Crick reveal the three-dimensional structure of DNA.
1954 Cell-culturing techniques are developed.
1955 An enzyme involved in the synthesis of a nucleic acid is isolated
for the first time.
1956 The fermentation process is perfected in Japan.
Kornberg discovers the enzyme DNA polymerase I, leading to an
understanding of how DNA is replicated.
1957 Sickle cell anemia is shown to occur due to a change of a single
amino acid.
1960 Exploiting base pairing, hybrid DNA-RNA molecules are created.
Messenger RNA is discovered.
1961 The genetic code is understood for the first time.
1964 The existence of reverse transcriptase (RT) is predicted.
1967 The first automatic protein sequencer is perfected.
1969 An enzyme is synthesized in vitro for the first time.
 Timeline Bioteknologi
1970 Specific restriction nucleases are identified, opening the way for gene cloning.
RT is discovered independently in murine and avian retroviruses.
1971 RT is shown to have ribonuclease H (Rnase H) activity.
1972 The DNA composition of humans is discovered to be 99 percent similar to that
of chimpanzees and gorillas. Purified RT is first used to synthesize cDNA from
purified mRNA in vitro.
1973 Cohen and Boyer perform the first successful recombinant DNA experiment,
using bacterial genes.
1974 The National Institute of Health forms a Recombinant DNA Advisory Committee
to oversee recombinant genetic research.
1975 Colony hybridization and Southern blotting are developed for detecting specific
DNA sequences. The first monoclonal antibodies are produced.
1976 The tools of recombinant DNA are first applied to a human inherited disorder.
Molecular hybridization is used for the prenatal diagnosis of alpha thalassemia.
Yeast genes are expressed in E. coli bacteria.
1977 Genetically engineered bacteria are used to synthesize human growth protein.
1978 North Carolina scientists Hutchinson and Edgell show it is possible to introduce
specific mutations at specific sites in a DNA molecule.
1979 The first monoclonal antibodies are produced.
 Timeline Bioteknologi
1980 The U.S. patent for gene cloning is awarded to Cohen and Boyer.
1981 The first gene-synthesizing machines are developed.
The first genetically engineered plant is reported.
Mice are successfully cloned.
1982 Humulin, Genentech's human insulin drug produced by genetically
engineered bacteria for the treatment of diabetes, is the first biotech
drug to be approved by the FDA.
1983 The Polymerase Chain Reaction (PCR) technique is conceived.
The first genetic transformation of plant cells by TI plasmids is
performed.
The first artificial chromosome is synthesized.
The first genetic markers for specific inherited diseases are found.
Efficient methods are developed to synthesize double-stranded DNA
from first-strand cDNA involving minimal loss of sequence information.
1984 The DNA fingerprinting technique is developed.
The first genetically engineered vaccine is developed.
Chiron clones and sequences the entire genome of the HIV virus.
1985 Fully active murine RT is cloned and overexpressed in E. coli.
 Timeline Bioteknologi
1986 The first field tests of genetically engineered plants
(tobacco) are conducted.
Ortho Biotech's Orthoclone OKT3, used to fight kidney
transplant rejection, is approved as the first monoclonal
antibody treatment.
The first biotech-derived interferon drugs for the treatment of
cancer, Biogen's Intron A and Genentech's Roferon A, are
approved by the FDA.
The first genetically engineered human vaccine, Chiron's
Recombivax HB, is approved for the prevention of hepatitis B.
1987 Humatrope is developed for treating human growth
hormone deficiency.
Genentech's tissue plasminogen activator (tPA), sold as
Activase, is approved as a treatment for heart attacks.
1988 Congress funds the Human Genome Project, a massive
effort to map and sequence the human genetic code as well as
the genomes of other species.
1989 Amgen's Epogen is approved for the treatment of renal
 Timeline Bioteknologi
1990 The first approved gene therapy treatment for immune disorder.
1991 Amgen develops Neupogen, for the treatment of low white blood
cells in chemotherapy patients.
Immunex's Leukine, used to replenish white blood counts after bone
marrow transplants, is approved.
Genzyme's Ceredase is approved for the treatment of Gaucher's
disease.
1992 The three-dimensional structure of HIV RT is elucidated.
Recombinate, used in the treatment of hemophilia A
Chiron's Proleukin is approved for the treatment of renal cell cancer.
1993 Chiron's Betaseron is approved as the first treatment for multiple
sclerosis .
The FDA declares that genetically engineered foods are "not inherently
dangerous" and do not require special regulation.
1994 Genentech's Nutropin is approved for the treatment of growth
hormone deficiency.
The first breast cancer gene is discovered.
1995 The first baboon-to-human bone marrow transplant is performed on
an AIDS patient.
 Timeline Bioteknologi
1996 Biogen's Avonex is approved for the treatment of multiple
sclerosis.
Scottish scientists clone identical lambs from early embryonic
sheep.
1997 Scottish scientists report cloning a sheep, using DNA from
adult sheep cells.
A group of Oregon researchers claims to have cloned two
Rhesus monkeys.
A new DNA technique combines PCR, DNA chips, and a
computer program, providing a new tool in the search for
disease-causing genes.
1998 University of Hawaii scientists clone three generations of
mice from nuclei of adult ovarian cumulus cells.
Human skin is produced in vitro.
Embryonic stem cells are used to regenerate tissue and create
disorders mimicking diseases.
A rough draft of the human genome map is produced, showing
the locations of more than 30,000 genes.
1999 The complete genetic code of the human chromosome is
first deciphered.
 Timeline Bioteknologi
2000 A rough draft of the human genome is completed by Celera
Genomics and the Human Genome Project.
Pigs are the next animal cloned by researchers, hopefully to
help produce organs for human transplant.
"Golden Rice," modified to make vitamin A, promises to help
third-world countries alleviate blindness.
2001 The sequence of the human genome is published in Science
and Nature, making it possible for researchers all over the
world to begin developing treatments.
2002 Scientists complete the draft sequence of the most
important pathogen of rice, a fungus that destroys enough rice
to feed 60 million people annually. By combining an
understanding of the genomes of the fungus and rice,
scientists will elucidate the molecular basis of the interactions
between the plant and pathogen.
2003 Dolly, the cloned sheep that made headlines in 1997, is
euthanized after developing progressive lung disease. Dolly
was the first successful clone of a mammal.
 Tingkatan Bioteknologi
State of the Art
1. LOW BIOTECHNOLOGY
Volume besar dengan produk atau jasa bernilai rendah (Low value high
volume)
Investasi murah, skala operasi kecil menengah, labour intensive, sistem
nonsteril, teknologi pedesaan / home industry
Pemurnian air, pengolahan limbah cair dan sampah, gas metan, etanol,
biomas (PST) atau pakan ternak

2. MIDLE BIOTECHNOLOGY
Volume relatif besar dengan produk bernilai ekonomi menengah (Midle value
and volume)
Investasi menengah, sistem operasi tidak terlalu rumit
Makanan minuman fermentasi, pakan ternak, biofertilizer, biopestisida, crude
enzyme

3. HIGH BIOTECHNOLOGY
Volume kecil dengan nilai ekonomis yang tinggi pula (High value low volume)
Investasi tinggi, pabrik dan sistem operasi rumit, terkontrol
Antibiotika, vaksin, antibodi, enzim dan vitamin
Nilai Strategis Bioteknologi

1. Pertambahan populasi manusia yang tidak

dapat diimbangi dengan pertambahan
produksi bahan kebutuhan hidup yang
dihasilkan secara konvensional.
2. Menipisnya sumber alam yang tidak dapat
diperbaharui
3. Keberlimpahan keanekaragaman sumber gen
di alam yang belum dimanfaatkan secara
maksimal oleh manusia.
4. Perkembangan IPTEK manusia yang
mengarah pada peningkatan efektivitas dan
efisiensi serta nilai ekonomis
IKHTISAR SKEMATIS PROSES BIOTEKNOLOGI

SELEKSI
ORGANISME

GENETIKA TERAPAN
Mutasi, rekombinasi, manipulasi gen,
transformasi gen, kloning

Udara Energi

PRODUK
BAHAN BIOREAKTOR
BAKU Atau
Mikrobial, sel
Seleksi, hewan, sel JASA
Sterilisas Dowstream
persiapan, tanaman, enzim
i process
perlakuan
Hea atau
t Recovery FORMULASI
PENGENDALIAN
PROSES
Biotech: Present & Future
 Transfer of new Anti-cancer drugs
Culture of plants
genes into animal from single cells Diagnostics
organisms

Cell Monoclonal
Culture Antibodies
Crime solving
Molecular
Biology

DNA Tracers
technology Genetic
Engineering
Synthesis of
Banks of Cloning specific DNA
DNA, RNA Synthesis
probes
and proteins of new Mass prodn. of
proteins human proteins
Complete Localisation of
New types of Resource bank
map of the genetic disorders
plants and for rare human
human
animals chemicals
genome
New
New types antibiotics
of food Gene therapy
Fakta Industri Bioteknologi
Biotechnology is a $30 billion a year industry that
has produced some 160 drugs and vaccines.
There are more than 370 biotech drug products and
vaccines currently in clinical trials targeting more
than 200 diseases, including various cancers,
Alzheimers disease, heart disease, diabetes, multiple
sclerosis, AIDS and arthritis.
Biotechnology is responsible for hundreds of medical
diagnostic tests that keep the blood supply safe from
the AIDS virus and detect other conditions early enough
to be successfully treated. Home pregnancy tests are
also biotechnology diagnostic products.
Genetic engineering is sweeping the worlds farms.
Seven million farmers in 18 countries grew genetically
engineered crops on 16.72 million acres last year.
Consumers already are enjoying biotechnology foods
such as papaya, soybeans and corn. Hundreds of
biopesticides and other agricultural products also are
being used to improve our food supply and to reduce
Fakta Industri Bioteknologi
Environmental biotechnology products make it
possible to clean up hazardous waste more efficiently by
harnessing pollution-eating microbes without the use of
caustic chemicals.
Industrial biotechnology applications have led to
cleaner processes that produce less waste and use less
energy and water in such industrial sectors as
chemicals, pulp and paper, textiles, food, energy, and
metals and minerals. For example, most laundry
detergents produced in the United States contain
biotechnology-based enzymes.
DNA fingerprinting, a biotech process, has
dramatically improved criminal investigation and
forensic medicine, as well as afforded significant
advances in anthropology and wildlife management.
There are 1,473 biotechnology companies in the
United States, of which 314 are publicly held.
Market capitalization, the total value of publicly
traded biotech companies (U.S.) at market prices, was
Fakta Industri Bioteknologi
The biotechnology industry has mushroomed since
1992, with U.S. revenues increasing from $8 billion in
1992 to $39.2 billion in 2003.
The U.S. biotechnology industry employed 198,300
people as of Dec. 31, 2003.
Biotechnology is one of the most research-intensive
industries in the world. The U.S. biotech industry spent
$17.9 billion on research and development in 2003.
The top eight biotech companies spent an average of
$104,000 per employee on R&D in 2003.
The biotech industry is regulated by the U.S. Food and
Drug Administration (FDA), the Environmental Protection
Agency (EPA) and the Department of Agriculture (USDA)
Designer Jeans: Made by
Microbes?
Stone-washing: Trichoderma
Cotton: Gluconacetobacter
Debleaching: Mushroom peroxidase
Indigo: E. coli
Plastic: Bacterial polyhydroxyalkanoate
 Stone washing denim
Indigo dye adheres
to denim surface
traditional new method
method

Cellulase enzyme
Denim is faded by removes some of the dye
abrasive action of by partially hydrolyzing the
pumice stones cotton surface

new looks
weakens the fabric lower costs
shorter treatment times
less solid waste
 Detergents
Detergent industry is the largest single market for
enzymes at 25 - 30% of total sales
Dirt comes in many forms and includes proteins,
starches and lipids (fats and oils)
proteases, amylases, lipases are enzymes used in
detergents
enzymes allows lower temperatures and less
agitation for washing
Inner core of enzyme plus
preservative bound with CMC

Protective waxy coat that

disperses in the wash
Industrial Chemicals
Examples:
organic acids produced from Aspergillus niger,
citric acid used in soft drinks
Xylanase used for wood pulping and bleaching
Agricultural
Examples:
Recombinant bovine somatotropin (bST) for
increasing milk production
Bio-insecticides for crop protection
Phyto-vanilla(tm) flavor derived from tissue
culture
The Birth of Modern
Chemotherapy
Treatment with chemicals is chemotherapy
Chemotherapeutic agents used to treat infectious
disease can be synthetic drugs or antibiotics
Antibiotics are chemicals produced by bacteria
and fungi that inhibit or kill other microbes
The First Synthetic Drugs
Quinine from tree bark was long used to treat
malaria
Paul Erlich speculated about a magic bullet
that could destroy a pathogen without harming
the host
1910: Ehrlich developed a synthetic arsenic drug,
salvarsan, to treat syphilis
1930s: Sulfonamides were synthesized
Microbial Ecology
Bacteria recycle carbon, nutrients, sulfur, and
phosphorus that can be used by plants and
animals
Biotechnology
Recombinant DNA technology, a new
technique for biotechnology, enables bacteria and
fungi to produce a variety of proteins including
vaccines and enzymes
Missing or defective genes in human cells can be
replaced in gene therapy
Genetically modified bacteria are used to protect crops
from insects and from freezing
 Mutant strains of bacteria and fungi
that synthesize large amounts of
metabolites
Primary metabolites - produced
during major metabolic pathways and
are essential to microbes function
amino acids, organic acids synthesized
during logarithmic growth
Secondary metabolites by-
products of metabolism that may not
be critical to microbes function 123
Insert figure 26.35
Origins of metabolites

124
 Many syntheses occur in
sequential fashion involving more
than one organism.
Biotransformation waste
product of one organism becomes
the building block of the next

125
Insert figure 26.36
biotransformation

126
Contoh Produk Fermentasi :

127
 Aerobasidium pullulans Pullulan

Xantomonas campestris Xanthan

Kultur Jaringan Tanaman
Aplikasi Kultur Jaringan
Tanaman
Kultur Sel Tanaman
GMOs
 Whats the link?

DNA, Gene, Transgenic, Clone, Genetically Modified

Genetic Disorder : Detecting and
Diagnosing Human Disease Conditions

DOWN SYNDROME
Down Syndrome
Medical Products and Applications of
Biotechnology
Gene Therapy
 Phytosensor : plants to detect
landmines

No TNT induction +TNT

Using inducible
promoter/GFP
fusions